The MXI1 tumor suppressor gene is not mutated in primary prostate cancer.
For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occurring genetic event. During the development of several human malignancies, the c-myc proto-oncogene has been identified to enhance cellular transformation, mitogenesis and cell proliferation. The MXI1 gene, belonging to the helix-loop-helix (bHLH) gene family, was demonstrated to display tumor suppressor function by antagonizing c-myc induced transcriptional activities. Due to the detection of point mutations in the retained alleles of four primary adenocarcinomas of the prostate, MXI1 gene alterations have been suggested to be involved in the development and/or the progression of prostate cancer. To evaluate the role of MXI1 gene alterations for the development of adenocarcinoma of the prostate, 42 primary prostate cancers of different stage (T1-4) and histological grade (G1-3) were investigated for alterations within exons 4 and 5 of the MXI1 gene (spanning 6 exons in total), encoding for the functional HLH-Zip domain, by RNA-SSCP analysis and direct PCR-DNA-sequencing following the microscopically guided tumor cell dissection from 5 microm fresh-frozen buffer-soaked tissue sections. Even by application of this highly elaborated technical approach, MXI1 gene alterations could not be deleted in any of the tumor specimens investigated. Therefore, a substantial involvement of MXI1 gene alterations in the development of prostate cancer appears unlikely. The newly identified putative tumor suppressor gene PTEN, located at #10q23, might be responsible for the frequently observed allelic deletions from #10q23-25 in prostate cancer.
Kuczyk
M A
MA
Department of Urology, Hannover University Medical School, Germany.
Serth
J
J
Bokemeyer
C
C
Schwede
J
J
Herrmann
R
R
Machtens
S
S
Grünewald
V
V
Höfner
K
K
Jonas
U
U
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000483:Alleles; D051792:Basic Helix-Loop-Helix Proteins; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C000715470:MAS1 protein, human; C079440:MXI1 protein, human